Biomimetic Chromatography Profiling of a Neurotoxicology-Relevant Compound Panel: A Physicochemical Dataset for New Approach Methodologies.

Developmental and adult neurotoxicity are hard to assess with conventional in vitro assays, which rarely account for how a chemical actually distributes once inside the body. Biomimetic chromatography offers a practical way to fill that gap, using stationary phases that mimic phospholipid membranes and major plasma proteins to yield experimental descriptors of lipophilicity, membrane affinity, and protein binding without needing radiolabeled compounds or large sample amounts. Working within the Partnership for the Assessment of Risk from Chemicals, we profiled 67 neurotoxicology-relevant chemicals on immobilized artificial membrane, human serum albumin, and alpha-1-acid glycoprotein columns alongside lipophilicity measured at three pH values. The chromatographic lipophilicity scale matched literature log p values closely. Principal component and hierarchical cluster analyses of the seven descriptors pointed to one dominant hydrophobicity axis and a smaller, second axis tied to ionization and albumin binding. The panel's overall chromatographic profile did not separate neurotoxic from non-neurotoxic reference compounds, but the most membrane- and protein-avid compounds were disproportionately positive controls and warrant closer attention. The resulting dataset gives New Approach Methodologies a ready, experimentally grounded input for in vitro-to-in vivo extrapolation and baseline toxicity assessment.